E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastroesophageal Reflux Disease (GERD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017924 |
E.1.2 | Term | Gastroesophageal reflux |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the effect of AZD3355 65 mg twice daily (bid) as add-on treatment to a Proton Pump Inhibitor (PPI) on GERD symptoms in patients with an incomplete response to PPI treatment with respect to improvement of each of the patient reported symptoms: - a burning feeling behind the breastbone (heartburn) - unpleasant movement of material upwards from the stomach (regurgitation)
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E.2.2 | Secondary objectives of the trial |
· To explore the effect of AZD3355 in patients with GERD symptoms and an incomplete response to PPI treatment with respect to additional patient reported symptoms · To estimate the effect of AZD3355 in patients with GERD symptoms and an incomplete response to PPI treatment with respect to consumption of antacids · To assess the pharmacokinetics of AZD3355 in patients with GERD symptoms · To assess the safety and tolerability during 4 weeks treatment with AZD3355 in patients with GERD symptoms and an incomplete response to PPI treatment · To explore the incidence of and the patients’ perception of paresthesiae and conditions with impaired wakefulness/alertness during 4 weeks treatment with AZD3355 · To explore the relationship between patient reported symptoms and perceived overall treatment effect, symptom control and treatment satisfaction, respectively
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent 2. Male or female (females must be post-menopausal, ((i.e >12 months without a menstrual period and > 50 years of age)) or be bilaterally oophorectomized or hysterectomized 3. Age 18-70 years 4. Weight 60-100 kg 5. At least 6 months history of GERD symptoms (need not to be consecutive) and a history of an incomplete response to PPI treatment 6. Continuously treated with an approved dose of any PPI during at least 6 weeks before enrolment 7. Ability to read and write and to use the e-diary 8. Screening questionnaire (RDQ) indicating a burning feeling behind the breastbone with a frequency of at least 3 days over the past 7 days and with at least mild intensity and/or unpleasant movement of material upwards from the stomach with a frequency of at least 3 days over the past 7 days and with at least mild intensity
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E.4 | Principal exclusion criteria |
1. Screening questionnaire (RDQ) indicating a equal or higher intensity of pain in the centre of the upper stomach than for a burning feeling behind the breastbone, if not fulfilling the inclusion criteria regarding unpleasant movement of material upwards from the stomach. 2. History of clinically significant cardiovascular, respiratory, renal, hepatic, neurological, mental or gastrointestinal (excluding GERD) disease. Patients with uncomplicated and well controlled Diabetes Mellitus and patients with uncomplicated and well controlled hypertension (SBP ≤160 mmHg and DBP ≤90 mmHg) can be included. 3. S-creatinine >1.2 times upper limit of normal (based on laboratory results from visit 1) 4. History of clinically significant orthostatic reactions 5. Systolic blood pressure below 110 mmHg 6. History of heart disease (eg, ischemic heart disease, congestive heart failure, cardiac arrhythmias) or signs or symptoms of heart disease including QTc >480 ms or other ECG abnormalities 7. Prior surgery of the upper GI tract (open, endoscopic and laparoscopic surgery on the esophagus, the stomach and the duodenum with the exception of oversewing or endoscopic treatment of an bleeding ulcer). 8. History of severe allergy/hypersensitivity or symptoms/signs of ongoing allergy/hypersensivity 9. Need for concomitant medication with - Drugs that may interfere with the pharmacodynamic effect of Investigational Product (eg, baclofen) - Drugs that may influence gastrointestinal symptoms, (eg, H2 receptor antagonists, sucralphate, alginates, tegaserod, metoclopamid, drugs with significant anticholinergic effect, non-steroid anti-inflammatory drugs (NSAIDs), cyclo-oxygenase-2 (COX-2) inhibitors, acetylsalicylic acid (ASA) >160 mg, biphosphonates, antineoplastic drugs) with exception of the PPI and antacids used in the study - Drugs that have a narrow therapeutic window (eg warfarin, digoxin, phenytoin, karbamazepin) - Drugs that may prolong the QT interval (see supplement for common examples) 10. History of drug addiction, alcohol abuse or other circumstances which in the investigators judgement may compromise the patient’s ability to comply with the study requirements 11. Any other condition which in the opinion of the investigator would render the patient unsuitable for inclusion in the study 12. Blood donation within 4 weeks prior to administration of the first dose of the investigational product 13. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 14. Administration of any investigational product or participation in any clinical study within 8 weeks prior to administration of the first dose of the investigational product 15. Previous enrolment or randomization of treatment in the present study.
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E.5 End points |
E.5.1 | Primary end point(s) |
For the Reflux Disease Questionnaire (RDQ) item(s) a burning feeling behind the breastbone and unpleasant movement of material upwards from the stomach, separately and in combination: - Number of days without symptom(s) - Maximum intensity during each week
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |